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Mutations in the DNMT3A exon 23 independently predict poor outcome in older patients with acute myeloid leukemia: a SWOG report

Leukemia volume 27, pages 238–241 (2013)Cite this article

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Acute myeloid leukemia (AML) represents a heterogeneous group of malignancies with great variability in clinical course and response to therapy. Currently, cytogenetics is the single most important prognostic factor in this disease. In recent years, an increasing number of molecular features with prognostic significance in AML have been identified.1, 2, 3

DNA cytosine-5-methyltransferase 3A (DNMT3A) encodes an enzyme that catalyzes the addition of a methyl group to the cytosine residue of CpG dinucleotides. By regulating the methylation of clusters of CpG, this enzyme mediates the downregulation of downstream genes. Recent studies using large-scale array-based genomic resequencing and whole-genome sequencing of human leukemia uncovered recurrent mutations in this gene in AML patients.4, 5 Subsequent studies demonstrated that these mutations are independently associated with decreased survival in adult AML patients.5, 6, 7, 8, 9, 10, 11 As the previous studies included mostly young AML patients, currently there is a paucity of information regarding the prognostic value of these newly identified mutations in the older AML population. Thus, we studied the incidence and prognostic impact of these mutations in the context of other prognostic markers in a cohort of uniformly treated older patients with AML.

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Acknowledgements

We thank the patients and families who consented to the use of biologic specimens in these trials and the AML Reference Laboratories of the COG and SWOG for providing diagnostic specimens. This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, Cancer Therapy Evaluation Program, DHHS: CA32102, CA38926, CA20319, CA12213.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    F Ostronoff, P A Ho, D E Geraghty, J P Radich, F R Appelbaum, D L Stirewalt & S Meshinchi

  2. Division of Medical Oncology, Seattle Cancer Care Alliance/University of Washington School of Medicine, Seattle, WA, USA

    F Ostronoff, S H Petersdorf, J P Radich, F R Appelbaum & D L Stirewalt

  3. SWOG Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    M Othus

  4. Division of Pediatric Hematology/Oncology, University of Washington School of Medicine, Seattle, WA, USA

    P A Ho & S Meshinchi

  5. Division of Pediatric Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    M Kutny

  6. Southern Illinois University Cancer Institute, Springfield, IL, USA

    J E Godwin

  7. UNM Cancer Research Facility, University of New Mexico Cancer Research and Treatment Center, Albuquerque, NM, USA

    C L Willman

Authors
  1. F Ostronoff
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  2. M Othus
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  3. P A Ho
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  4. M Kutny
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  6. S H Petersdorf
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  9. J P Radich
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  10. F R Appelbaum
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  11. D L Stirewalt
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Correspondence to F Ostronoff.

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The authors declare no conflict of interest.

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Author contribution

FO designed and performed the research, analyzed data and wrote the manuscript; MO performed statistical analyses and edited the manuscript; PAH, DEG, SHP, JEG, CLW, JPR and FRA performed the research and edited the manuscript; SM designed the research, analyzed data and edited the manuscript.

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Ostronoff, F., Othus, M., Ho, P. et al. Mutations in the DNMT3A exon 23 independently predict poor outcome in older patients with acute myeloid leukemia: a SWOG report. Leukemia 27, 238–241 (2013). https://doi.org/10.1038/leu.2012.168

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